The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD–PanZ·AcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan),Biochemistry

当前位置： X-MOL 学术 › Biochemistry › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

The Mechanism of Regulation of Pantothenate Biosynthesis by the PanD–PanZ·AcCoA Complex Reveals an Additional Mode of Action for the Antimetabolite N-Pentyl Pantothenamide (N5-Pan)
Biochemistry ( IF 2.9 ) Pub Date : 2017-09-07 00:00:00 , DOI: 10.1021/acs.biochem.7b00509
Zoe L. P. Arnott _{1,

2} , Shingo Nozaki ₃ , Diana C. F. Monteiro _{1,

2} , Holly E. Morgan ₁ , Arwen R. Pearson ₂ , Hironori Niki _{3,

4} , Michael E. Webb ₁

Affiliation

The antimetabolite pentyl pantothenamide has broad spectrum antibiotic activity but exhibits enhanced activity against Escherichia coli. The PanDZ complex has been proposed to regulate the pantothenate biosynthetic pathway in E. coli by limiting the supply of β-alanine in response to coenzyme A concentration. We show that formation of such a complex between activated aspartate decarboxylase (PanD) and PanZ leads to sequestration of the pyruvoyl cofactor as a ketone hydrate and demonstrate that both PanZ overexpression-linked β-alanine auxotrophy and pentyl pantothenamide toxicity are due to formation of this complex. This both demonstrates that the PanDZ complex regulates pantothenate biosynthesis in a cellular context and validates the complex as a target for antibiotic development.

中文翻译：

PanD–PanZ·AcCoA复合物调节泛酸生物合成的机制揭示了抗代谢物N-戊基泛酸酰胺（N5-Pan）的另一种作用方式。

抗代谢戊戊泛酰胺具有广谱抗生素活性，但对大肠杆菌的活性增强。已经提出通过限制响应辅酶A浓度的β-丙氨酸的供应来调节PanDZ复合物在大肠杆菌中的泛酸生物合成途径。我们表明活化天冬氨酸脱羧酶（PanD）和PanZ之间的这种复合物的形成导致螯合丙酮酸辅因子作为酮水合物，并证明PanZ过表达连锁的β-丙氨酸营养缺陷和戊基泛酰胺的毒性均是由于这种形成复杂的。这都证明了PanDZ复合物在细胞环境中调节了泛酸的生物合成，并证实了该复合物是抗生素开发的目标。

更新日期：2017-09-07

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11